Liothyronine (T3), along with its precursor levothyroxine (T4), have often been prescribed, alone or in combination, for the initial treatment of clinical underactive thyroid in hormone replacement therapy. Underactive thyroid, is the prevalent disease-state hypothyroidism, a common condition in which the thyroid gland neglects to produce sufficient amounts of thyroid hormones. This condition precipitates life-altering, and potentially life threatening symptomology in approximately 5.8 million people within the United States, as reported by the American Association of Clinical Endocrinologists (AACE) including ataxia, intractable chronic fatigue, bradycardia, cold intolerance, hyperlipidemia, mental impairment, weight gain, impaired concentration, and depression.
Currently, T3 is commercially available as 5, 25, and 50 microgram immediate-release (IR) tablets of liothyronine sodium (Cytomer), which are typically administered up to 2-4 times daily. T3 is a biologically active moiety that is rapidly absorbed into the bloodstream with a high reported bioavailability (69-99%). T3 is 3-4 times more potent as compared to T4; yet exhibits a relatively short half-life of less than 2 days, versus that of T4 (6-7 days). Thus, following the administration of any IR formulation, T3 plasma levels often fluctuates, which leads to inconsistent and often undesired serum levels. In addition, some patients can be under or over treated using the only available three dosages.
The benefits and drawbacks of commercially available formulations of T3 have been studied in the past. Recent studies have also reviewed the effectiveness of T4 and T3 as the single active ingredient versus a fixed amount of T3 and T4 as a combination therapeutic. Most recently, it has been shown that a slow-release T3 or a specific blend of T4 with slow-release T3 may grant more benefit to the patients and resolve many of the limitations on patients' quality of life. These results indeed have highlighted the individual needs of patients and have brought to the spotlight the fact that one size does not fit all. Compounded T4, T3, or a combination thereof at mathematical ratios other than 4.22:1 can help a certain patient population who otherwise will be therapeutic failures.
Despite available hormone replacement therapy stategies, still a significant percentage of patients with hypothyroidism and thyroid dysfunctionality remain symptomatic. There is continued need in the art for sustained release T3 formulations that maintain stable concentrations of T3, such that daily administration of T3 provides steady serum levels of T3.